The objective of this project is to examine the role of mucopeptide, a structure common to the cell wall of many bacteria, in the pathogenesis of rheumatoid arthritis. Previous investigators have demonstrated that animals immunized systemically with streptococcal vaccines develop IgM and IgG rheumatoid factors (Bokisch et al, 1972). Some of the IgG rheumatoid factors possessed specificity for mucopeptide antigens (Bokisch et al, 1973b). Also, if the cell wall fragments were injected into rabbit knees, a destructive synovitis developed (Schwab et al, 1967). The presence of mucopeptide antigens within the synovial macrophages corresponded to the persistence of the synovitis. Our background data indicate that antibodies to a portion of the mucopeptide, pentapeptide, are increased in the sera of patients with rheumatoid arthritis. We propose to extend these studies, examining additional sera and synovial fluids for antibodies to the streptococcal mucopeptide and to synthetic pentapeptide, which is structurally identical to the pentapeptide found in the Group A variant streptococcal mucopeptide. Radioimmunoassays for antibodies to the isolated mucopeptide and the synthetic pentapeptide will be performed on samples from normal volunteers and patients with rheumatoid arthritis, acute rheumatic fever, juvenile rheumatoid arthritis and systemic lupus erythematosus. Additionally, antibodies will be isolated by immunoadsorbant chromatography to determine if a portion of the patient's rheumatoid factor cross reacts with the mucopeptide antigen. Such a finding would strongly implicate these bacterial antigens in the initiation of rheumatoid factors and possibly the immune complexes found in patients with rheumatoid arthritis. Additionally, rheumatoid synovial tissue will be examined for the presence of mucopeptide antigens, which in experimental animals are poorly degraded by macrophages and which correlate in these animals with the course of the experimental synovitis. Our studies will hopefully delineate the factors responsible for the initiation of rheumatoid arthritis.